A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+breast cancer: A National Cancer Database analysis

Background Small invasive breast cancers (BCs) with tumor sizes <= 5 mm (T1a) are associated with an excellent prognosis without systemic therapy. Although HER2 overexpression (HER2+) is associated with a higher risk of recurrence and poorer clinical outcomes, in the absence of HER2 directed therapy, it remains unclear whether adjuvant systemic therapy is necessary in node-negative patients diagnosed with HER2+ invasive BCs <= 5 mm (pT1aN0M0). Methods The National Cancer Database was searched to identify patients diagnosed with HER2+ pT1aN0M0 BCs from 2004 to 2017. The cohort was stratified by treatment status: local therapy alone or local plus adjuvant systemic therapy. A 1:1 propensity match was performed. Overall survival (OS) was analyzed using stratified multivariable Cox proportional hazards regression analyses. Results Of the 8948 patients found, 4026 (45.0%) underwent surgery alone, and 4922 (55.0%) received surgery plus systemic therapy. Patients with either moderately differentiated (odds ratio [OR], 2.053; P < .001) or poorly/undifferentiated tumors (OR, 3.780; P < .001) or with the presence of lymphovascular invasion (OR, 3.351; P < .001) were more likely to have received systemic therapy. Propensity matching generated 1162 pairs of patients who were hormone receptor positive (HR+) and 748 pairs who were hormone receptor negative (HR-). Propensity matching effectively reduced selection bias between study groups. In the matched cohort, the addition of systemic therapy was not associated with superior OS (hazard ratio for HR+, 1.613; P = .107, and hazard ratio for HR- 1.319; P = .369) compared with patients who received local therapy alone. Conclusions In pT1aN0M0 HER2+ BC, the addition of adjuvant systemic therapy after surgical excision was not associated with improved OS compared with local therapy alone.